Hypertension is to be studied at levels from whole animal hemodynamics to subcellular events. The primary goal is to define the cause of the increase in total peripheral resistance. Swine with renal hypertension and one leg protected from the increase in arterial pressure and wall stress by occlusion of the external iliac artery will be studied at 5 levels: 1) Hemodynamic changes during the development of renal hypertension will be monitored by measuring cardiac output and arterial pressure and calculating total peripheral resistance. We anticipate the initiating event may be an increase in cardiac output which, within a few days, will give way to an increase in total peripheral resistance. 2) At intervals during the progress of the hypertension parallel constant flow perfusion studies of the two hind legs will permit a definition of neurogenic vascular tone, non-neurogenic vascular tone, and structural resistance following complete relaxation of the vascular smooth muscle. Vascular reactivity to several constrictor agents will be evaluated by dose-response studies. 3) Isolated strips from small resistance vessels (100 u o.d. or smaller), large conduit arteries (3 plus or minus mm) and veins will be used to evaluate vascular smooth muscle reactivity and contractility. 4) Techniques previously used in our laboratory will evaluate (a) contractile protein function, (b) uptake and efflux of calcium from microsomal and mitochondrial fraction of vascular smooth muscle, and (c) active pumping of cations by the plasma membrane. 5) Possible structural correlates of functional changes will be looked for in small and large vessels of both the protected and unprotected legs, using light and electron microscopy.